The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference.
Neuropeptide Y (NPY) is a 36-amino-acid peptide hormone abundantly expressed both in the central and peripheral nervous systems. NPY plays a central role in the hypothalamic regulation of food intake and energy expenditure. Central administration of NPY markedly stimulates feeding, and chronic infusion results in development of obesity, hyperinsulinemia and insulin resistance in experimental animals. Relatively little is known of the role of NPY in human obesity or metabolic diseases.
Neuropeptide Y (NPY), a member of a family of peptides, is a neurotransmitter, which is widely expressed both in the central and peripheral nervous systems.sup.1,2. Several regulatory functions have been implicated to NPY including feeding.sup.3,4,5, anxiolysis.sup.6,7, pituitary hormone release.sup.8,9,10, thermogenesis.sup.11 and insulin release.sup.12.
In animals NPY plays an important role in the hypothalamic regulation of energy balance. NPY markedly stimulates food intake after central administration.sup.13. It also decreases energy expenditure by decreasing brown adipose tissue thermogenesis, and favors energy storage by increasing lipoprotein lipase activity in white adipose tissue.sup.14. Chronic intracerebroventricular infusion of NPY results in the development of obesity and insulin resistance.sup.13. Food restriction markedly enhances hypothalamic NPY activity, while re-feeding decreases it, and the hypothalamic NPY neurons are controlled by peripheral hormonal feedback signals, like insulin and leptin.sup.14,15,16. Consequently, hypothalamic expression of preproNPY mRNA and NPY levels are elevated in obese fa/fa Zucker rat.sup.17, which have impaired leptin signaling due to a point mutation in the leptin receptor gene.sup.18. In humans, NPY concentrations in the cerebrospinal fluid of anorexia patients are elevated.sup.19, which is consistent with the putative compensatory activation of NPY mechanisms. Importantly anorexia patients also show elevated cholesterol levels.sup.20,21. However no reports were available from the literature connecting NPY gene or NPY as such to cholesterol metabolism or serum cholesterol levels.